Cardiovascular diseases, including hypertension, are the No. 1 lethal factor in the world, and are known as the “First Killer against Human Health”. At present, anti-hypertensive drugs available in the market are mainly divided into the following categories: diuretics (thiazide drugs), β-receptor blockers (-lol drugs), calcium antagonists (dipine drugs), angiotensin converting enzyme (ACE) inhibitors (pril drugs), Angiotensin II-receptor antagonists (sartan drugs). Among patients with hypertension, only 25% cases can be controlled with existing drugs. Aliskiren is the first non-peptide renin inhibitor approved by FDA in 2007, which attains vasodilation and blood pressure lowering effects by inhibiting renin activity and thereby decreasing the levels of angiotensin I and angiotensin II. A unique feature of Aliskiren is: it can inhibit plasma renin activity (PRA), which not only is a risk factor for myocardial infarction of patients with hypertension, but also is closely related with target organ damage. Decreasing PRA is helpful for protection of the target organ. That feature is an important feature that differentiates renin inhibitor drugs from other antihypertensive drugs.
Aliskiren was originally developed by Novartis, the chemical compound patent is U.S. Pat. No. 5,559,111A, and the synthetic route is shown as follows:

Two key intermediate compounds I and II are involved in the route.
In U.S. Pat. No. 5,559,111A, the compound I is obtained from compound III, and Ph3P, NBS by controlling the raw materials to react in methylene chloride (solvent) at room temperature for 16 hours, evaporating the solvent, and conducting column chromatography for the residue; the yield is 50%˜60%. No other synthetic methods for compound I have been described in any other literatures, except for this method.

In existing literatures (Tetrahedron Letters, 46 (2005), 6337; Helvetica Acta, 86 (2003), 2867), the method for preparation of compound II is as follows:

The compound II is obtained from compound IV and Ph3P, NBS by controlling the raw materials to react in methylene chloride (solvent) at room temperature for 21 hours, evaporating the solvent, and conducting column chromatography for the residue; the yield is 50%˜60%.
The methods for preparation of compounds I and II described above are difficult to be used in industrial production and the yield of the product is low, because the final product has to be separated and purified by column chromatography.